The gene markers have been identified for the major families which have been followed. Longitudinal data collection, expansion of pedigree information and recruitment of additional family members and families have been continued as well as counseling of numerous families, some followed since 1977. Emphasis will continue, comparing longitudinal clinical study data, and familial and psychosocial factors with DNA and pathological findings. Accomplishments for the year are as follows: Because of the FAD-1 family's involvement, we were able to further define the amyloid (AB-42) which precedes other types in the cascade of neuropathology secondary to presenilin 1-linked Alzheimer Disease; with the 13 year follow-up of 22 twin pairs, we were able to add credence to the impact of hormonal and infectious contributions to AD and decrease the credence in traumatic factors; and tissue from some of the families being followed helped further the understanding of presenilin and amyloid precursor protein genes in Alzheimer disease and ruled out the R406W tau mutation in progressive supranuclear palsy and corticobasal degeneration.